Helper T cells are broadly divided into two types: those that invoke cellular inflammatory (TH1) responses; and those that drive humoral (TH2) immunity, including allergic-like reactions to large pathogens, such as parasitic worms. These two classes of response are generally incompatible with one another and require coordination by cytokines to promote one while dampening the other.

Interleukin (IL)-18 was originally characterized through its ability to co-induce IFNγ expression by TH1 cells, but two studies now suggest that this cytokine has much broader functions. Neighbors et al. observed that IL-18 exerted a major influence on primary and secondary immune responses to the bacterium Listeria monocytogenes in mice. Indeed, IL-18 displayed even greater potency than the two principal TH1-promoting cytokines IL-12 and IFNγ. IL-18 achieved this potency partly through the induction of the antimicrobial agents TNFα and nitric oxide. In a model of helminth infection, Helmby et al. found that IL-18 suppressed the cytokine IL-13. IL-13 is a major factor mediating expulsion of parasitic worms from the gut. Thus, alongside potent antimicrobial effects, IL-18 can negatively influence the course of TH2 immunity. — SJS